The chemistry of N-substituted-1,2,3-triazoles has been well developed due to its high biological activity, however, the preparation of isomeric pure N-substituted-1,2,3-triazoles is not trivial. Direct alkylation of 1(H)-1,2,3-triazoles forms mixtures of 1- and 2-substituted 1,2,3-triazoles, which are often difficult to separate, and once formed often undergo isomerization equilibria in solution. Cycloaddition reactions usually lead to 1-substituted-1,2,3-triazoles. However, this synthesis route is complicated by the use of hazardous reagents, e.g., organic azides and acetylenic materials. High yields of 1-vinyl-1,2,3-triazole and 1-isopropyl-1,2,3-triazole have been reported, however the use of expensive 1(H)-1,2,3-triazole is required.
Heterocyclic compounds based on 1,2,3-triazoles have been widely employed due to their high biological activity, in antiviral, antimicrobial, antifungal medicines and agricultural chemicals. Other applications include photo-chemicals, corrosion inhibitors, and dyes. Previously, various routes for preparation of 1(H)-1,2,3-triazole have been reported. However, processes are complicated and overall yields are low. JP #05140121, 07278121, 07126257 and U.S. Pat. No. 5,478,947 describe the use of tosylhydrazide, glyoxal and ammonia to produce 1(H)1,2,3-triazole. The best reported overall yield is about 67%, however processes are very complicated and produce a lot of waste. U.S. Pat. No. 5,728,841 describes a method of preparing of 1(H)-1,2,3-triazole, through diazotization of 1-amino-1,2,3-triazole, however the best yield reported is 57%.
Recently, a patent application on new ionic liquids described the formation of 1-substituted-4-amino-1,2,4-triazolium salts from the alkylation of 4-amino-1,2,4-triazole with alkyl halides (Drake et al 2002). 1-amino-1,2,3-triazole is an isomer of 4-amino-1,2,4-triazole and it has been found to form a class of low melting salts many of which fit under the definition of ionic liquids. These ionic liquids have found a wide array of applications ranging from solvents and catalysts to energetic materials.
Heterocycles with high nitrogen content typically have high heats of formation, high densities, but can often have significant toxicities. Through the use of heterocyclic salt based materials, much of this toxicity can be significantly reduced for safer handling and exposure.
For the most pharmaceutical intermediates purity is a crucial factor, especially, when it comes to isomerical purity. Due to the completely different behavior of the different isomers in biological systems, preparation of desired isomers, not contaminated with other isomers is important. Preparation of isomerically pure N-substituted-1,2,3-triazoles is not trivial. Direct alkylation of 1(H)-1,2,3-triazoles forms mixtures of 1- and 2-substituted 1,2,3-triazoles, which are often difficult to separate, and once formed often undergo isomerization equilibria in solution. Cyclo-addition reactions usually lead to 1-substituted-1,2,3-triazoles, however this synthetic route is complicated by the use of hazardous explosive and sensitive reagents, e.g. organic azides and terminal acetylenes. U.S. Pat. No. 6,642,390 notes these drawbacks, but still employs organic azides in the synthesis of 1,2,3-triazole carboxylic acids. High yields of 1-vinyl-1,2,3-triazole, and 1-isopropyl-1,2,3-triazole have been reported, however the use of expensive 1(H)-1,2,3-triazole is required.
An object of the present invention is to provide a scalable process for preparing a novel class of 3-substituted-1-amino-triazolium salts and subsequently, 1-substituted-1,2,3-triazoles.
Accordingly, there is need and market for a low cost method of preparation of certain substituted triazoles which overcome the above prior art shortcomings.
There has now been developed a substituted triazolium salt, a new compound, and subsequently preparing therefrom 1-substituted-1,2,3-triazoles, a new method.